Process for making a porous substrate of glass powder formed through flame spray pyrolysis

ABSTRACT

Inorganic porous substrates and methods of making inorganic porous substrates utilizing nanoparticles deposited onto a base substrate are described. The inorganic porous substrates are useful for biological applications, for example, biomolecule attachment such as DNA, RNA, protein and the like. The inorganic porous substrates are also useful for cell growth applications.

This application claims the benefit of priority to provisionalapplication No. 60/926,248, titled “Process for Making a PorousSubstrate of Glass Powder Formed Through Flame Spray Pyrolysis,” filedon Apr. 26, 2007, attorney docket no. SP07-073P, the contents of whichare incorporated by reference herein in their entirety.

BACKGROUND

1. Field of the Invention

The present invention relates generally to inorganic porous substratesand more particularly to a method of making inorganic porous substratesutilizing nanoparticles deposited onto a substrate.

2. Technical Background

Over the years, there has been rapid progress in the areas ofelectronics, materials science, and nanoscale technologies resulting in,for example, smaller devices in electronics, advances in fibermanufacturing and new applications in the biotechnology field. Theability to generate and collect increasingly smaller, cleaner and moreuniform particles is necessary in order to foster technological advancesin areas which utilize small particulate matter. The development of new,efficient and adaptable ways of producing small particulate matter andsubsequently collecting or depositing the small particulate matter ontoa substrate becomes more and more advantageous.

The size of a particle often affects the physical and chemicalproperties of the particle or material comprising the particle. Forexample, optical, mechanical, biochemical and catalytic properties oftenchange when a particle has cross-sectional dimensions smaller than 200nanometers (nm). When particle sizes are reduced to smaller than 200 nm,these smaller particles of an element or a compound often displayproperties that are quite different from those of larger particles ofthe same element or compound. For example, a material that iscatalytically inactive in the macroscale can behave as a very efficientcatalyst when in the form of nanoparticles.

The aforementioned particle properties are valuable in many technologyareas. For example, in optical fiber manufacturing, the generation ofsubstantially pure silica and germanium soot particles from impureprecursors in a particular size range (about 5-300 nm) has been key inproviding optical preforms capable of producing high purity opticalfiber. Also, in the field of pharmaceuticals, the generation ofparticles having certain predetermined properties is advantageous inorder to optimize, for example, in vivo delivery, bioavailability,stability of the pharmaceutical and physiological compatibility. Theoptical, mechanical, biochemical and catalytic properties of particlesare closely related to the size of the particles and the size of thecompounds comprising the particles.

Porous microstructures are of great interest to many research andcommercial areas. Three-dimensional structures made from nanoparticlesprovide optimum surface area. Enhanced surface area is an enablingphysical property for many applications, such as custom spottedmicroarrays, high display of surface area for catalysis, high display ofluminescent elements and the like. Conventional methods of producingenhanced surface area, such as the method described in PCT PublicationNo. WO0116376A1 and commonly owned US Patent Application PublicationNos. 2003/0003474 and 2002/0142339, the disclosures of which areincorporated herein by reference in their entirety, use ball milledCorning 1737™ glass particles of size range from 0.5 □m to 2 □m. Theseball milled particles are sintered onto Corning 1737™ glass substrates.

The conventional ball milling processes for manufacturing slides for usein the manufacture of microarrays have the following disadvantages: lotto lot variability between ball milled preparations of 1737™microparticles, broad heterogeneous particle size distributions,requirement for post processing deposition of the ball milledmicroparticles by either tape casting or screen printing, particle sizesare especially large and do not yield ultimate nanoparticle surfaceareas, screen printing has been shown to yield missing spot effects onmicroarrays due to irregular surface patterns and limitation of theprocess to 1737™ glasses.

It would be advantageous to have methods for producing particles in thenanometer size range (average particle sizes 500 nm or less) thusminimizing the size variation and composition variation evident inconventional ball milling processes for making inorganic poroussubstrates.

SUMMARY

Methods for making porous substrates of the present invention aredescribed herein. The methods address one or more of the above-mentioneddisadvantages of conventional ball milling methods and conventionalaerosol particle generating methods, in particular, when the desiredparticles are dimensionally in the nanometer range (average particlesize of 500 nm or less).

Methods for producing a porous substrate comprising average particlesizes of 500 nanometers or less using flame spray pyrolysis aredescribed herein. In some embodiments, the average particle sizes are,for example, 400 nm or less, 300 nm or less, 200 nm or less, 100 nm orless or 80 nm or less.

In one embodiment, a method of depositing nanoparticles onto a basesubstrate to produce an inorganic porous substrate using flame spraypyrolysis is described. The method comprises providing a solutioncomprising glass precursors and a solvent, atomizing the solution toform aerosol droplets, synthesizing nanoparticles from the aerosolparticles using a flame and either subsequently or simultaneouslysintering the nanoparticles onto the base substrate.

According to another embodiment, a method of making a coated inorganicporous substrate is described. The method comprises providing a solutioncomprising glass precursors and a solvent, atomizing the solution toform aerosol droplets, passing the aerosol droplets through a flameunder conditions sufficient to generate nanoparticles, depositing thenanoparticles onto a base substrate to form the inorganic poroussubstrate, and coating the inorganic porous substrate with a materialselected from a silane, a polymer and combinations thereof.

Another embodiment is a method comprising providing a solutioncomprising glass precursors and a solvent, atomizing the solution toform aerosol droplets, passing the aerosol droplets through a flameunder conditions sufficient to generate nanoparticles, depositing thenanoparticles onto a base substrate to form an inorganic poroussubstrate, coating the inorganic porous substrate with a materialselected from a silane, a polymer and combinations thereof, anddepositing a biomolecule onto the coated inorganic porous substrate.

Additional features and advantages of the invention will be set forth inthe detailed description which follows, and in part will be readilyapparent to those skilled in the art from the description or recognizedby practicing the invention as described in the written description andclaims hereof, as well as the appended drawings.

It is to be understood that both the foregoing general description andthe following detailed description are merely exemplary of theinvention, and are intended to provide an overview or framework tounderstanding the nature and character of the invention as it isclaimed.

The accompanying drawings are included to provide a furtherunderstanding of the invention, and are incorporated in and constitute apart of this specification. The drawings illustrate one or moreembodiment(s) of the invention and together with the description serveto explain the principles and operation of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention can be understood from the following detailed descriptioneither alone or together with the accompanying drawing figures.

FIG. 1 is a scanning electron microscope (SEM) photomicrograph ofnanoparticles deposited onto a substrate comprising surface area of 176m2/g.

FIG. 2 is an X-ray diffraction plot of the nanoparticles of FIG. 1.

FIG. 3 is a photograph of nanoparticles deposited onto a base substratethat is a glass microscope slide.

FIG. 4 is a photograph of nanoparticles deposited onto a base substratethat is a microwell format.

FIG. 5 is an SEM photomicrograph of the morphology of an inorganicporous substrate on a 1737™ slide in cross-section after being sinteredat 800° C. for 2 hours in air atmosphere.

FIG. 6 is an SEM photomicrograph of the morphology of an inorganicporous substrate on a 1737™ slide after being sintered at 800° C. for 2hours in air atmosphere.

FIG. 7 is an SEM photomicrograph of the morphology of an inorganicporous substrate on a 1737™ slide after being sintered at 800° C. for 2hours in air atmosphere.

FIG. 8 shows Cy3/Cy5 signal-to-noise bioassay data for two poroussubstrates made according to the present invention on slides.

FIG. 9 shows an image of hybridized microarrays printed on two poroussubstrates made according to the present invention on slides as comparedto a control porous substrate (left) made according to a conventionalattrition ball milled and screen printing process on a slide.

DETAILED DESCRIPTION

Reference will now be made in detail to various embodiments of theinvention, examples of which are illustrated in the accompanyingdrawings. Wherever possible, the same reference numbers will be usedthroughout the drawings to refer to the same or like parts.

According to one embodiment, a solution is provided, for example, atroom temperature, comprising glass precursors such as components of amulticomponent glass, for example, Si, Al, B, Ca, Mg, Sr, K, Ba, Ni andCo. The glass precursors are organic derivatives that will pyrolyze totheir corresponding oxides. The glass precursors are dissolved in aflammable solvent, such as an alcohol. Organic solvents that could beused include methanol, ethanol, propanol, higher alcohols (including allpossible isomers of carbon chains), methoxy-alcohols, alkoxy-alcohols,hydrocarbon solvents (e.g. mineral spirits), ketones (e.g. acetone),ethers (e.g. dimethyl ether, methyl-ethyl ether) or mixtures thereof.

The solution is converted by atomizing into a spray of aerosol droplets.Atomizing can be achieved by a variety of methods, for example, throughan external mixing air-assisted nozzle. The spray of aerosol droplets isconverted into oxide nanoparticles using flame spray pyrolysis, whereinthe composition of each particle is determined by the composition of theliquid which is atomized.

The conversion to oxide nanoparticles is facilitated through theaddition of heat. A source of flammable gas can also be used inconjunction with the heat in some applications. For example, a source ofoxygen, methane, propane or combinations thereof, or any flammable gas.Sources of heat comprise combustion by ignition of the flammable spraywith a flame or a spark. The oxide nanoparticles are then deposited ontoa substrate to form an inorganic porous substrate.

Table 1 shows examples of liquid compositions of the solution used togenerate nanoparticles according to one embodiment. The solutions wereprepared in a nitrogen filled drybox to minimize particulate formationduring mixing due to hydrolysis of the glass nanoparticle precursorsupon exposure to moist air. The order of mixing of the composition glassnanoparticle precursors can affect the properties of the resultingsolution and thus the glass nanoparticle precursors were mixed aspresented in Table 1 (top to bottom). Glass precursors for SiO₂, Al₂O₃,B₂O₃, CaO, MgO, SrO, K₂O and BaO can include tetraethylorthosilicate,aluminum tri-sec-butoxide, boron-tri-ethoxide, calcium 2-methoxyethoxidein 2-methoxyethanol, magnesium 2-methoxyethoxide in 2-methoxyethanol,strontium iso-propoxide, potassium tert-butoxide and bariummethoxypropoxide in methoxypropanol respectively. The solution accordingto the embodiment illustrated in Table 1 also comprises anhydrousethanol, 18 MΩ/cm water (as an alternative, other purity of water can beused either more pure or less pure) and 2 M HCl. In another embodiment,glass precursors for NiO, Co₃O₄ were added to the solution. Theseprecursors were Nickel(II) acetylacetonate and Cobalt(III)acetylacetonate respectively. The solution comprising the glassnanoparticle precursors and the solvent was stirred until the solidglass nanoparticle precursors were dissolved, in order to minimizeplugging of the atomizer.

A commercial external air-assisted atomizer (Schlick AtomizingTechnologies model 970 S4) was used in conjunction with a flame sprayburner and incorporated into a nanoparticulate generating apparatus. Theflame spray burner was used to generate a pilot flame that ignites theflammable spray comprising the solution and combustible gases. Theburner conditions used were as follows: a flow of methane at a rate of3.6 L/min, a flow of oxygen at a rate of 3.4 L/min, a flow of nitrogenshield gas at a rate of 10 L/min. The conditions at the nozzle of theatomizer were as follows: a flow of atomizing oxygen at a rate of 25L/min, a differential pressure across the nozzle of 1 Bar and a liquidflow rate of solution at a rate of 7.5 mL/min. Oxide nanoparticles weredeposited directly onto 1737™ substrates in either 96-well format or1″×3″ slide format.

The 1737™ substrates were placed in a chamber and exposed to theair-borne soot (oxide nanoparticles) generated by the burner beforeventing to a wet scrubber particle pollution abatement system. Afterdeposition, the slides were heated in an air atmosphere furnace for 2hours at 750° C. to fix the oxide nanoparticles to the substrate bypartial sintering.

According to other embodiments, the deposited oxide nanoparticles can besintered onto the substrates at temperatures of 700° C. or more, or attemperatures of 750° C. or more, or at temperatures of 800° C. or more,or at temperatures of 850° C. or more or at temperatures of 900° C. ormore depending on the composition of the oxide nanoparticles and theintended application.

TABLE 1 Composition 1 2 Mass or Mass or Chemical Volume Moles VolumeMoles Tetraethylorthosilicate 64.4 g 0.3092 64.4 g 0.3092 (99.95%,Chemat Technology) Anhydrous ethanol (Pharmco 480 g 10.42 480 g 10.42Products, Inc.) 18 MΩ/cm water 4.0 g 0.222 4.0 g 0.222 2 M HCl (FisherScientific) 2.2 mL — 2.2 mL — Aluminum tri-sec-butoxide 10.6 g 0.04310.6 g 0.043 ((97%, Aldrich Chemicals) Boron-tri-ethoxide (Avocado 57.2g 0.3918 57.2 g 0.3918 Research Products) 20 wt % calcium 2- 8.14 g0.00856 8.14 g 0.00856 methoxyethoxide in 2- Ca Ca methoxyethanol(Geleste, Inc.) 25 wt % magnesium 2- 1.8 g 0.00258 1.8 g 0.00258methoxyethoxide in 2- Mg Mg methoxyethanol (Geleste, Inc.) Potassiumtert-butoxide 1.7 g 0.0151 1.7 g 0.0151 (95-99%, Strem Chemicals)Strontium iso-propoxide 1.4 g 0.0068 N/A N/A (Geleste, Inc.) Bariumiso-propoxide (Strem 1.8 g 0.00704 N/A N/A Chemicals) 19 wt % strontiumN/A N/A 9.52 g 0.0068 methoxypropoxide in methoxypropanol (Geleste,Inc.) 25 wt % barium N/A N/A 8.88 g 0.00704 methoxypropoxide inmethoxypropanol (Geleste, Inc.)

Table 2 shows normalized oxide nanoparticle compositions (analysis wasdone on bulk powders comprising the nanoparticles which are commensuratewith the compositions deposited on the porous substrate by ICP MassSpectroscopy) resulting from the flame spray pyrolysis method of thesolutions described in Table 1 according to one embodiment.

TABLE 2 Wt % (Target) 1 2 SiO₂ 64.88 66.68 63.06 Al₂O₃ 7.68 7.68 7.36B₂O₃ 18.19 16.62 19.83 CaO 1.53 1.34 1.45 MgO 0.36 0.34 0.39 SrO 0.941.05 2.27 K₂O 2.74 2.58 2.09 BaO 3.68 3.68 3.51

Table 3 shows the experimentally determined wt % of compositions 3, 4, 5and 6 of oxide nanoparticles produced by the combustion of the solutionand flammable spray utilizing flame spray pyrolysis according to anotherembodiment. The oxide nanoparticle compositions include adsorbedcombustion products, which comprise approximately 7 to 9 weightpercentages (wt %). When the oxide nanoparticle compositions are heatedat a temperature of 700° C. or more, the combustion products areminimized as shown by differential thermal analysis. Therefore, theweight percentages of components are normalized to 100% to representelemental ratios in the bulk oxide nanoparticle compositions.

TABLE 3 Experimental Data Normalized Normalized wt % Target 3 4 5 6 SiO₂63.95 61.8 66.23724 59.1 64.830927 Al₂O₃ 7.57 7.07 7.577626 6.967.6349112 B₂O₃ 17.93 13.8 14.79084 14.8 16.235156 CaO 1.51 1.52 1.6291361.45 1.5906065 MgO 0.35 0.35 0.37513 0.34 0.3729698 SrO 0.93 0.880.943184 0.85 0.9324245 K₂O 2.7 2.81 3.011758 2.79 3.0605463 BaO 3.633.66 3.922788 3.53 3.8723041 NiO 1.01 1 1.0718 0.95 1.0421215 Co₃O₄ 0.40.41 0.439438 0.39 0.4278183 sum 99.98 93.3 99.99894 91.16 99.9997852

Nanoparticles were generated and deposited onto a substrate using themethods described above. FIGS. 1 and 2 illustrate that the exemplifiedporous substrate comprising nanoparticles (analysis was done on bulkpowders comprising the nanoparticles which are commensurate with thecompositions deposited on the porous substrate) is amorphous and glassy,as shown by the first peak 2 of the X-ray diffraction plot. The secondpeak 3 shows a minor component B(OH)₃ which is a crystalline phase ofboric acid. This minor component is removed upon sintering of theinorganic porous substrate. The deposited nanoparticles 1 areapproximately 80 nm in mean diameter and have a surface area ofapproximately 170 m²/g.

According to another embodiment, increased control over particlecollection efficiency and particle packing density can be achieved byheating the substrates during deposition and/or can be facilitatedthrough electrostatic deposition methods. For example, a charge can beprovided on the base substrate by placement of the base substratebetween two oppositely charged electrodes and/or a charge can be inducedon the nanoparticles by charging the particles using a corona charger orother charging techniques known in the art. Exemplary electrostaticmethods and apparatuses are described in commonly owned U.S. patentapplication Ser. No. 11/712,149, the disclosure of which is incorporatedherein by reference in its entirety.

According to another embodiment, the base substrate can be heated duringthe deposition process at temperatures of 400° C. to 800° C. duringdeposition in order to increase the deposition of the nanoparticles orto increase the particle packing or densification of the poroussubstrate.

The deposited oxide nanoparticles can be thermally adhered (sintered)onto the base substrate either by heating during the deposition processor as a subsequent and separate step. Further densification of thesurface can be subsequently done for certain applications throughadditional heat treatments of the inorganic porous substrate.

The sintering process is achieved by heating the inorganic poroussubstrates under appropriate conditions such as temperature, duration ofheating and rate of cooling. These conditions are selected for theappropriate oxide being sintered. Local heat generation for sinteringcan be achieved by oven bake, CO₂ LASER sinter and microwave sinter.Other methods for forming interparticle connections may include wetmethods as are known in the art, such sol-gel methods.

The base substrate can comprise a slide 4 or a microplate 6 format asshown in FIG. 3 and FIG. 4 respectively. Slides are typically 1 inch by3 inches. Nanoparticles can be deposited onto substrates which comprisea microplate insert format. Typical microplate insert formats are 3inches by 4.5 inches.

According to another embodiment, prior to depositing the nanoparticlesonto the base substrate, a portion of the base substrate can be maskedsuch that a pattern of inorganic porous substrate is formed on the basesubstrate.

A mask, for example, a stainless steel plate can have holes drilled in amicroplate format, for example, 96 or 384 well formats. The mask withholes can be positioned between the base substrate and the airbornenanoparticles such that the nanoparticles are deposited only on theunmasked areas. After deposition, the mask can be removed and the poroussubstrate comprising areas of deposited nanoparticles 5 can be sinteredand/or coated. A holey plate can then be adhered to the base substrateforming a microwell plate such that the deposited nanoparticles arelocated at the bottom of some or all of the wells of the microwellplate.

FIG. 5, FIG. 6 and FIG. 7 illustrate the morphology of the poroussubstrate 7 comprising oxide nanoparticles deposited onto a microscopeslide substrate 8 and sintered at 800° C. for 2 hours in an airatmosphere furnace. The structure of the sintered nanoparticles isweb-like, resulting from the viscous flow and/or surface diffusion ofthe nanoparticles during heat treatment (e.g. sintering). In thisembodiment, the sintering process causes the nanoparticles to form aseries of interconnected webs 11 defining interconnected pores 10located between the webs. The interconnected pores defined by theinterconnected webs transverse the width of the porous substrate from afirst surface 23 of the porous substrate to a first surface 22 of thesubstrate.

The interconnected webs range in size from 0.1 to 1 microns. Theinterconnected pores defined by the webs are 25 microns or less and thethickness of the porous substrate is from 8 to 10 microns. FIG. 5 showsthe porous substrate in cross-section comprising interconnected pores.FIG. 6 shows the porous substrate (topical view) comprisinginterconnected pores 9 which are 20 microns or less in size. In someembodiments, the interconnected pores are 5 microns or less in size.FIG. 7 shows the porous substrate comprising interconnected webs 11 andinterconnected pores 10 which are 1 micron or less in size.

This interconnected web and interconnected pore microstructure isadvantageous in that it provides a more uniform distribution ofmaterial, for example, biological material, silane, cells and the likewhen the material is coated onto the porous substrate.

Nanoparticles which are deposited onto the surface of a base substrateby the above-mentioned methods can undergo subsequent processing stepsdepending on the intended application.

According to another embodiment, after sintering, the inorganic poroussubstrates can be subsequently coated with a number of materials, forexample, polymers and silanes to form a coated porous substrate. Thecoated porous substrates are useful for covalent or non-covalentattachment of biomolecules.

Silanes have been shown to modify the surface characteristics of glassand to subsequently affect the interaction of the surface withbiological molecules (e.g. DNA, proteins, and even cells). Silanes canbe used to provide either covalent attachment chemistry for theretention of DNA or a non-covalent retention of DNA by chargeattraction. In some cases, multiple characteristics of the silanemolecules can be used to provide a hydrophobic, as well as chargedsurface, which can also be used to attach DNA either covalently ornon-covalently. Examples of silane molecules which can provide thehydrophobic charged surface are (but not limited to) aminefunctionalized silanes (e.g. GAPS™ 3-aminopropyltrimethoxy silane(trademark of Corning Incorporated),N-(2-aminoethyl)-3-aminopropyltrimethoxy silane) or thio functionalizedsilanes (3-mercaptopropyltrimethoxysilane). These silanes can be usedalone or in combination to coat the inorganic porous substrates of thepresent invention.

Silane coating can be performed either by solution phase coating or CVDcoating. The solution coating process involves either dip coating orimmersing the inorganic porous substrate into an organic carrier solventsuch as isopropyl alcohol (IPA) and a percentage by volume of silane.The silane is allowed time to coat and then the process is stopped byremoval of the inorganic porous substrate from the coating bath and isfollowed by subsequent wash steps. The CVD process involves placing thedry nanoparticle surface into a sealed coating chamber and then allowingexposure of a silane vapor that is generated by either heat or vacuum.

One example of a non-covalent attachment of plasmid DNA to nanoparticlesis shown in FIG. 8 and FIG. 9. FIG. 8 shows Cy3/Cy5 signal-to-noisebioassay data for two inorganic porous substrate microarrays 12 and 13made according another embodiment of the present invention as comparedto a control porous substrate microarrays 14 made according to aconventional attrition ball milled and screen printing process. FIG. 9shows the image of the hybridized microarrays printed on two inorganicporous substrates 16 and 17 made according to the present invention ascompared to a control porous substrate 15 made according to aconventional attrition ball milled and screen printing process.

Biomolecules can be deposited onto the inorganic porous substratesaccording to the present invention by a number of deposition techniquesas are known to one skilled in the art of microarray manufacturing, forexample, printing with pins, quills or printing from a reserviorcomprising biomolecules. For example, biomolecules can be suspended in abioassay solution. The pins are introduced into the bioassay solution.When the pins are withdrawn from the bioassay solution, some of thebiomolecules are adhered to the pins. The pins then contact the coatedinorganic porous substrate and the biomolecules are transferred to thecoated inorganic porous substrate. This process is repeated multipletimes and a microarray format of printed spots of biomolecules isproduced.

The defect “missing spots” can occur on a microarray for a number ofreasons such as the inability to distinguish the printed spot for thebackground noise of the coated inorganic porous substrate (referred toas signal-to-noise), the lack of biomolecules transferring to the coatedinorganic porous substrate during printing due to the surface roughnessof the coated inorganic porous substrate or due to a lack of uniformityin the coating of the coated inorganic porous substrate or a combinationthereof.

Preliminary data as evident in FIG. 8 and FIG. 9 indicates that theinorganic porous substrates made according to the present inventionresult in minimizing the “missing spots” problem inherent in theconventionally manufactured inorganic porous substrates. Thesignal-to-noise is also higher (lower background) in Cy3/Cy5 testscompared to conventional screen-printed attrition ball milled poroussubstrates. Porous substrates according to the present invention can beused for binding and functional assays, for example, of G-proteincoupled receptors (GPCR).

It will be apparent to those skilled in the art that variousmodifications and variations can be made to the present inventionwithout departing from the spirit or scope of the invention. Thus, it isintended that the present invention cover the modifications andvariations of this invention provided they come within the scope of theappended claims and their equivalents.

1. A method of depositing nanoparticles onto a base substrate to form aninorganic porous substrate, the method comprising: providing a solutioncomprising glass precursors and a solvent; atomizing the solution toform aerosol droplets; passing the aerosol droplets through a flameunder conditions sufficient to generate oxide nanoparticles; anddepositing the oxide nanoparticles onto a base substrate to form theinorganic porous substrate.
 2. The method according to claim 1, furthercomprising masking a portion of the base substrate such that a patternof inorganic porous substrate is formed on the base substrate.
 3. Themethod according to claim 2, wherein the pattern of inorganic poroussubstrate is a 96 well or 384 well pattern.
 4. The method according toclaim 1, wherein the solvent is selected from methanol, ethanol,propanol, alcohols, methoxy-alcohols, alkoxy-alcohols, hydrocarbonsolvents, ketones, ethers, methyl-ethyl ether and combinations thereof.5. The method according to claim 1, further comprising heating the basesubstrate at a temperature of 400° C. to 800° C. during deposition. 6.The method according to claim 1, further comprising providing a chargeon the base substrate.
 7. The method according to claim 1, furthercomprising heating the base substrate at a temperature of 700° C. ormore such that the oxide nanoparticles are simultaneously deposited andsintered onto the base substrate.
 8. The method according to claim 1,further comprising sintering the inorganic porous substrate at atemperature of 700° C. or more.
 9. The method according to claim 8,comprising sintering the inorganic porous substrate at a temperature of750° C. or more.
 10. The method according to claim 9, comprisingsintering the inorganic porous substrate at a temperature of 800° C. ormore.
 11. A method of making a coated inorganic porous substrate, themethod comprising: providing a solution comprising glass precursors anda solvent; atomizing the solution to form aerosol droplets; passing theaerosol droplets through a flame under conditions sufficient to generateoxide nanoparticles; depositing the oxide nanoparticles onto a basesubstrate to form the inorganic porous substrate; and coating theinorganic porous substrate with a material selected from a silane, apolymer and combinations thereof.
 12. A method comprising: providing asolution comprising glass precursors and a solvent; atomizing thesolution to form aerosol droplets; passing the aerosol droplets througha flame under conditions sufficient to generate oxide nanoparticles;depositing the oxide nanoparticles onto a base substrate to form aninorganic porous substrate; coating the inorganic porous substrate witha material selected from a silane, a polymer and combinations thereof;and depositing a biomolecule onto the coated inorganic porous substrate.13. The method according to claim 12, wherein the depositing abiomolecule onto the coated porous substrate comprises printing of thebiomolecule.
 14. The method according to claim 13, wherein the printingof the biomolecule is selected from pin printing, quill printing andreservoir printing.
 15. The method according to claim 12, wherein thebiomolecule is selected from DNA, RNA, protein and combinations thereof.16. The method according to claim 15, wherein the biomolecule comprisesa G-protein coupled receptor.